{
  "abstract": "Background: The progression of hepatocellular carcinoma (HCC) is significantly influenced by the tumor microenvironment, in which cancer-associated fibroblasts (CAFs), collagen fibers (CFs), and tumor-infiltrating lymphocytes (TILs) interact to regulate tumor growth and immune infiltration. Understanding the spatial and functional coordination among these components is essential for prognostic assessment.\n\nMethods: This retrospective study included 335 patients from two tertiary hospitals. Early-stage HCC tissue samples were analyzed using artificial intelligence-based algorithms to quantify TIL fraction and aggregation, while collagen architecture was characterized using multiphoton microscopy (MPM). Moreover, single-cell RNA sequencing was used for functional profiling of CAFs, and multiplex immunofluorescence was applied for spatial validation. The relationship between TILs and collagen features was associated with clinical outcomes. Prognostic models were developed using Cox regression and validated internally and externally.\n\nResults: MPM demonstrated strong co-localization of CFs and TILs, with lymphocytes spatially aligned following collagen orientation within the tumor core. CAF subtypes exhibited heterogeneous expression of extracellular matrix (ECM)-related and lymphocyte-modulatory genes, with ECM-mediated signaling dominating CAF–T/B cell communication. TIL aggregation and CF orientation independently predicted disease-free and overall survival. The multifactorial Fiber-TIL-Clinical model (FTC model) achieved superior predictive performance (area under the curve = 0.902 for early recurrence) by integrating these features with clinical variables.\n\nConclusions: The FTC model integrates CF features and TIL characteristics, demonstrating strong performance in predicting HCC recurrence.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12967-026-08686-x.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Pathology, The Affiliated Union Hospital of Fujian Medical University, Fuzhou, China",
    "Department of Hepatobiliary Pancreatic Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, 350001 China",
    "School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China",
    "School of Arts and Sciences, Fujian Medical University, Fuzhou, China",
    "Key Laboratory of OptoElectronic Science and Technology for Medicine of Ministry of Education, Fujian Provincial Key Laboratory of Photonics Technology, College of Photonic and Electronic Engineering, Fujian Normal University, Fuzhou, 350007 China",
    "Fujian Provincial Hospital, Shengli Clinical Medical College of Fujian Medical University, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian China",
    "Fuzhou University Affiliated Provincial Hospital, 134 Dongjie Street, Fuzhou, Fujian Province China"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuan’e Lian"
    },
    {
      "affs": [
        1
      ],
      "name": "Zehong Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Dongsheng Xia"
    },
    {
      "affs": [
        1
      ],
      "name": "Zhongchang Weng"
    },
    {
      "affs": [
        1
      ],
      "name": "Jiaying Ye"
    },
    {
      "affs": [
        1
      ],
      "name": "Siqin Zhang"
    },
    {
      "affs": [
        3
      ],
      "name": "Xingxing Huang"
    },
    {
      "affs": [
        4
      ],
      "name": "Lianhuang Li"
    },
    {
      "affs": [
        5
      ],
      "name": "Jie Lin"
    },
    {
      "affs": [
        1
      ],
      "name": "Songqiang Zhou"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Shi Chen"
    },
    {
      "affs": [
        1,
        6
      ],
      "name": "Yannan Bai",
      "orcid": "0000-0002-5862-281X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/86padhpp87yt7.bib",
  "cited_by": 0,
  "doi": "10.1186/s12967-026-08686-x",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13711724/",
  "id": "86padhpp87yt7",
  "issns": [
    "1479-5876"
  ],
  "landing_url": "https://doi.org/10.1186/s12967-026-08686-x",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2721|Hepatocellular Carcinoma Treatment and Prognosis"
    ]
  ],
  "openalex": "W7171866150",
  "pdf_url": null,
  "pmcid": "PMC13711724",
  "pmid": "42947199",
  "published": "2026-07-30",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/86padhpp87yt7.ris",
  "sources": [
    {
      "first_seen": "2026-10-31T12:22:27Z",
      "native_id": "PMC13711724",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12967-026-08686-x"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2721|Hepatocellular Carcinoma Treatment and Prognosis",
      "subfield": "general"
    }
  ],
  "title": "Cancer-associated fibroblasts shape features of lymphocyte aggregation and collagen deposition in hepatocellular carcinoma",
  "title_text": "Cancer-associated fibroblasts shape features of lymphocyte aggregation and collagen deposition in hepatocellular carcinoma",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T12:22:27Z",
  "url": "https://research.draconitic.com/paper/86padhpp87yt7",
  "venue": "Journal of Translational Medicine",
  "versions": []
}